The Public Health Research Institute (PHRI) of New Jersey Medical School, Rutgers University, Newark, NJ, USA.
Department of Biological Sciences, NYC College of Technology, Brooklyn, NY, USA.
Eur J Immunol. 2020 Jun;50(6):858-872. doi: 10.1002/eji.201948448. Epub 2020 Mar 20.
Host protective immunity against pathogenic Mycobacterium tuberculosis (Mtb) infection is variable and poorly understood. Both prior Mtb infection and BCG vaccination have been reported to confer some protection against subsequent infection and/or disease. However, the immune correlates of host protection with or without BCG vaccination remain poorly understood. Similarly, the host response to concomitant infection with mixed Mtb strains is unclear. In this study, we used the rabbit model to examine the host response to various infectious doses of virulent Mtb HN878 with and without prior BCG vaccination, as well as simultaneous infection with a mixture of two Mtb clinical isolates HN878 and CDC1551. We demonstrate that both the ability of host immunity to control pulmonary Mtb infection and the protective efficacy of BCG vaccination against the progression of Mtb infection to disease is dependent on the infectious inoculum. The host response to infection with mixed Mtb strains mirrors the differential responses seen during infection with each of the strains alone. The protective response mounted against a hyperimmunogenic Mtb strain has a limited impact on the control of disease caused by a hypervirulent strain. This preclinical study will aid in predicting the success of any vaccination strategy and in optimizing TB vaccines.
宿主对致病性结核分枝杆菌（Mtb）感染的保护性免疫具有变异性，目前仍了解甚少。先前的 Mtb 感染和卡介苗（BCG）接种据称可提供针对随后感染和/或疾病的一定保护。然而，有无 BCG 接种时宿主保护的免疫相关性仍知之甚少。同样，宿主对混合 Mtb 菌株同时感染的反应也不清楚。在这项研究中，我们使用兔模型来研究在有无先前 BCG 接种的情况下，宿主对各种不同感染剂量的强毒 Mtb HN878 的反应，以及同时感染两种 Mtb 临床分离株 HN878 和 CDC1551 的混合物。我们证明，宿主免疫控制肺部 Mtb 感染的能力以及 BCG 接种预防 Mtb 感染进展为疾病的保护效果都取决于感染接种量。宿主对混合 Mtb 菌株的感染反应反映了单独感染每种菌株时的不同反应。针对高免疫原性 Mtb 菌株的保护性反应对控制由高毒力菌株引起的疾病的影响有限。这项临床前研究将有助于预测任何疫苗接种策略的成功，并优化结核病疫苗。
